From the Guidelines
Elevated liver enzymes are a significant indicator of potential liver disease, and their clinical significance should be evaluated in the context of the patient's overall health and medical history, as stated in the guidelines on the management of abnormal liver blood tests 1. The presence of elevated liver enzymes can be an indicator of various liver conditions, including non-alcoholic fatty liver disease (NAFLD), liver fibrosis, and cirrhosis. According to the guidelines, the next step in evaluating patients with NAFLD or liver disease of unknown etiology is to determine the likelihood of liver fibrosis using scores such as FIB-4 or NAFLD fibrosis score 1. Some key points to consider when evaluating elevated liver enzymes include:
- The degree of abnormality is not always related to the stage of progression from simple fatty liver to cirrhosis 1.
- Elevated liver enzymes can be dose-dependent and may occur in 0.5% to 2.0% of cases, as seen with statin use 1.
- The clinical significance of elevated liver enzymes should be evaluated in the context of the patient's overall health and medical history, as some patients may have underlying liver disease that is not immediately apparent 1.
- In patients with NAFLD, discontinuation rules for study drugs should be determined as multiples of baseline rather than multiples of ULN, to avoid premature discontinuations 1. It is essential to approach each patient with elevated liver enzymes on a case-by-case basis, considering their individual medical history, symptoms, and laboratory results to determine the best course of action. Prompt evaluation and management of elevated liver enzymes are crucial to prevent progression to liver failure and improve patient outcomes 1.
From the Research
Significance of Elevated Liver Enzymes
Elevated liver enzymes are a common finding in both symptomatic and asymptomatic patients, necessitating further evaluation to clarify the underlying disease 2. The significance of elevated liver enzymes can be understood by considering the different patterns of enzyme elevation, which can indicate various liver conditions.
Patterns of Enzyme Elevation
There are three different patterns of increased liver enzymes:
- A predominant increase in transaminase activities, which reflects a disturbance of hepatocellular integrity and can be found in patients with viral hepatitis, genetic liver diseases, and drug-induced liver diseases 2.
- A pattern characterized by high serum alkaline phosphatase and γ-glutamyltranspeptidase activities, indicating cholestatic liver diseases 2.
- A pattern defined by a predominant rise in γ-glutamyl transpeptidase, which is observed in alcoholic or non-alcoholic fatty liver disease and infiltrating liver diseases 2.
Causes of Elevated Liver Enzymes
The causes of elevated liver enzymes can be diverse, including:
- Viral hepatitis
- Genetic liver diseases (e.g., Wilson's disease, hemochromatosis)
- Drug-induced liver diseases
- Alcoholic liver disease
- Non-alcoholic fatty liver disease (NAFLD)
- Cholestatic liver diseases (e.g., primary and secondary sclerosing cholangitis)
- Infiltrating liver diseases
- Extrahepatic diseases (e.g., sepsis, bacterial infections) 2, 3, 4.
Evaluation and Management
The evaluation and management of elevated liver enzymes involve a step-wise approach, including:
- Interpretation of abnormal elevation of liver enzymes using a schematic approach that classifies enzyme alterations on the basis of pattern 5.
- Initial investigations, such as viral serology, autoantibodies, and abdominal ultrasound scan 4.
- A single-act office visit can be an efficient way to evaluate patients with elevated liver enzymes, yielding a diagnosis in most patients 4.
Clinical Implications
Elevated liver enzymes can have significant clinical implications, including:
- Indicating potential liver injury or disease 5.
- Requiring further evaluation and management to prevent progression of liver disease 2, 3.
- Being associated with increased mortality in patients with bacterial sepsis, although jaundice may indicate increased survival in elderly patients 3.
- Being a common finding in patients treated with immune checkpoint inhibitors, often with a cause other than immunotoxicity 6.